Electromagnetic radiation has been used in a wide array of noninvasive diagnostic applications. X-rays have been used for many years to create a two dimensional image of the inside of an object. Computed axial tomography scanners are able to generate three dimensional images from a series of two dimensional x-ray images. Magnetic resonance imaging (also known as nuclear magnetic resonance spectroscopy), such as disclosed in Harms et al., U.S. Pat. No. 5,415,163 A and Rapoport et al., U.S. Pat. No. 4,875,486 A, operate by first applying a magnetic field to a subject so as to align, in a uniform manner, the nuclei of atoms within a portion of the subject to be tested. These aligned nuclei are then briefly exposed to a radio frequency (RF) signal set to a specific frequency, which causes each of the various aligned nuclei at a lower energy state to spin or flip to a higher energy state, known as a resonant frequency. The magnetic field is then removed or altered, causing the nuclei forced to a resonant frequency to become unstable and return to their original lower energy state. This later process is called spin relaxation. The faint energy released from the spin relaxation is then collected as a representation of the nuclei within the sample.
Hence, the spin relaxation energy released by the sample is used to generate an image that is representative of the sample. The RF signal itself is not utilized for detection or imaging purposes—it is only used to excite the nuclei to a higher energy state and is removed before the spin relaxation energy is detected. Further, the magnetic field(s) are only used to align and then release the nuclei in the sample, and are removed or altered before spin relaxation can occur.
While electromagnetic signals transmitted through a specimen have been used to detect or measure the concentration of various chemicals in that specimen, such prior techniques were not highly accurate and results were often difficult to repeat. For example, U.S. Pat. No. 4,679,426 disclosed a non-invasive technique for measuring the concentration of chemicals, such as sodium chloride, in a sample. Periodic electromagnetic waves between 10 MHz and 100 MHz were coupled to a subject's finger and resulting waveforms were found to be indicative, at specific frequencies (i.e., 17.75 MHz for sodium chloride and potassium chloride), of concentration levels of those chemicals in the finger. Likewise, U.S. Pat. No. 4,765,179 used periodic electromagnetic waves between 1 MHz and 1 GHz, that were coupled to a subject's finger, to generate a waveform that provided meaningful analysis of glucose levels in the subject based on the presence of other compounds in the subject's blood at specific frequencies (i.e., 17.75 MHz for sodium chloride and potassium chloride, 11.5 MHz for ethyl alcohol, etc.).
In U.S. Pat. No. 5,508,203 (the “'203 patent”), high frequency electromagnetic radiation was coupled to a specimen through a probe pair to generate a signal of varying amplitude or phase that could be compared to a source signal to determine the presence of a target chemical, such as NaCl, to help determine glucose levels. While this later technique represented an improvement over the prior methods, it was soon realized that electrolytes, e.g., NaCl, KCl, Na2HPO4, and KH2PO4 of varying concentrations in human blood, can affect the accuracy of glucose measurements using the '203 patent.
To account for the deficiencies in the '203 patent, a new technique was developed in U.S. Pat. No. 5,792,668 (the “668 patent”), in which two signals were transmitted through the subject at the same time and the magnitude of impedance at the subject was measured to determine a glucose level in the subject. In particular, the two signals had a cross-over frequency of about 2.5 GHz that provided the best measurement of impedance. In blood specimens, it was found that electrolyte concentration effects are effectively “tuned out” by examining impedance at this cross-over frequency. A similar approach was applied in U.S. Pat. No. 7,184,810 (the “'810 patent”), which cites the '668 patent. In the '810 patent, a probe is applied to the subject's skin, through which electric pulses from a pulse generator are fed and partially reflected back to a measuring device, where a time resolved measurement is made. The glucose level is determined from matching the measured voltage to a calibration table.
The next evolutionary step in the development of electromagnetic energy signals to determine the presence and concentration level of chemicals within a subject is represented in U.S. Pat. No. 6,723,048 B2 (the “'048 patent”), which is assigned to the assignees of the present application and which discloses a noninvasive apparatus for analyzing blood glucose and similar characteristics. The '048 patent apparatus utilizes spaced apart transmission and detection nodes placed on either side of and in contact with a sample to be tested. The nodes are always in close proximity to one or more pairs of magnets that create a magnetic field that envelope the nodes and the sample between the nodes. An RF signal having a frequency between 2 GHz and 3 GHz is transmitted from the transmission node through the sample and to the detection node.
The detected signal is then sent to an analyzer that employs pattern recognition techniques to compare the detected signal at a specific frequency (with respect to glucose, the '048 patent specified 2.48 GHz), to previously detected signals at the same frequency to make a determination regarding the characteristic of the sample being tested. For example, if the sample was a finger of a patient that had previously been tested when the patient was known to have different glucose levels (verified through a more traditional form of glucose testing) to create three or more previously detected signal patterns, the presently detected signal would be compared to each of these previously detected signal patterns to determine which pattern it most closely resembled in order to approximate the patient's present blood glucose level.
In addition to testing glucose levels and other blood chemistries, it has been speculated that electromagnetic frequency spectrum technologies could have application to the biometric identification field, but development is still needed in this area. In many fields of activity, it is essential that persons be identified or their claimed identity be authenticated. Examples of such fields include granting physical access or entry into buildings, rooms or other spaces, airport security, credit card purchasers, ATM users, passport verification, electronic access to information or communication systems, etc.
A number of noninvasive detection technologies have been developed to address these needs, such as fingerprint scans, iris and retina scans, and voice recognition. These technologies operate on the principal that individuals possess unique and unchanging physical characteristics that can be measured and compared with stored data. The basic requirements for acceptable biometric technology are that it must allow for practical widespread use, be accurate and reliable, be difficult or impossible to circumvent, be quick, easy and convenient, present no or little privacy violation concerns, be low cost to produce, and be consumer friendly. Current biometric identification and authentication technologies do not meet all of these basic requirements.
Iris and retina scanning technologies can be highly accurate, but the equipment used in scanning is expensive and requires substantial space. Further, humans are highly uncomfortable with the idea of having their eyes scanned with a laser or infrared light or having their picture taken and stored by a machine (and then used by who knows who). Also, iris and retina scanners have been spoofed with a number of techniques that have required the technologies to be modified in various ways, making the technology more expensive, less convenient, and less consumer friendly.
Electronic or optical fingerprint scanning systems are inexpensive, but are not very accurate, are easily damaged, and can be easily spoofed. Variations in skin, ethnic races with very light fingerprint patterns, people with unusually dry skin, elderly people, people with rough hands, water webbing, abrasions and cuts have all been known to create difficulties for fingerprint systems. Furthermore, many people consider fingerprinting to be an invasion of their privacy because of the heavy use of fingerprinting for law enforcement purposes. Additionally, many fingerprint scanning devices have been easily spoofed with objects as common as gummy candy.
Voice recognition systems tend to be the least accurate of the other biometric identification and authentication technologies. Voices can be readily recorded or mimicked, and allergies, colds and other respiratory issues can readily produce false negatives. Hand geometry and face recognition systems suffer from similar issues. They also tend to require a large amount of space and face recognition systems can be expensive. As with fingerprints, changes in a subject's skin, such as a suntan, a burn or a skin condition, or other changes to a subject's physical appearance can present problems for the system.
Obesity is a major health problem in many countries and is associated with an increased risk for heart disease, certain cancers and development of Type II diabetes. Obesity is now so common within the world's population that it is beginning to replace under-nutrition and infectious diseases as the most significant contributor to ill health (Kopelman (2000) Nature 404: 635-643, which is incorporated herein by reference in its entirety). According to the Centers for Disease Control's (CDC's) National Center for Health Statistics, 54% of adult Americans and between 11% and 14% of children were overweight in 1997, as determined using the Body Mass Index (BMI) scale, which defines classes of non-obesity and obesity. According to the BMI scale, obesity is generally defined by a body-mass index (weight divided by square of the height) of 30 kg·m−2 or greater.
Behavioral interventions play a central role in treatment programs designed to promote lifestyle changes leading to weight management and improved physical fitness. Behavioral studies have shown that the keeping of detailed records, or self-monitoring, is considered one of the most essential features of behavior therapy (Baker & Kirschenbaum, (1993) Behavior Therapy 24: 377-394). Some of the earliest research on the behavioral effects of self-monitoring revealed that a subject's awareness of data collection during a study often caused a reactive process that influenced the behavior being observed (Gottman & McFall, (1972) Journal of Consulting and Clinical Psychology 39: 273-281). Additionally, these studies have suggested that the accuracy of the information obtained was not as important as self-focusing attention on the behavior (Baker & Kirschenbaum (1993)). Therefore, when it comes to weight management and physical performance enhancement, consistent self-monitoring appears to contribute to the desired outcomes more so than accurate self-monitoring.
Monitoring food intake plays an important role in any weight management program. Self-monitoring of dietary intake is consistently associated with adherence to dietary measures (Schnoll & Zimmerman, (2001) Journal of the American Dietetic Association 101: 1006-1011). The more consistently subjects self-monitored, the more weight they lost. This positive effect is seen throughout the literature—consistent self-monitoring of food intake is associated with a decrease in food intake and a subsequent weight loss.
Self-monitoring of physical activity, such as through the use of a diary, can be as important to one's health and physical performance as self-monitoring of food intake. These diaries typically include entries citing the duration of the exercise as well as the intensity of the activity. Furthermore, specific information may be tracked and recorded such as: the weather at the time of the activity, pain or discomfort encountered during the activity, or the number of sets or repetitions performed.
The quantity of blood sugar in a subject's body at any given point is representative of the calories they have consumed as well as utilized as a result of exercise or simply living. Consequently, a subject's blood sugar level correlates well to their weight or performance management. For example, if the subject's blood sugar levels are higher than normalized levels, they may be in a position to gain weight; if their blood sugar levels are lower than normalized levels, they may be in a position to lose weight. While this correlation is well known and incorporated into a number of weight management plans, prior art blood sugar testing devices have not made it practical to test a subject's blood sugar levels multiple times a day to help manage their caloric intake and utilization. An embodiment changes this situation, however, by enabling a user to carefully and painlessly test and manage their caloric intake and utilization many times during the course of a day, thereby enabling use by anyone desiring to control their weight, including athletes, dieters, etc.
Likewise, an athlete's performance could be optimized through use of such a device by carefully monitoring blood sugar levels to make sure the athlete had the optimum amount of fuel for energy in their body at a needed time.
By coupling the blood scanning features of an embodiment to a computer equipped with additional weight management software, a user could track their weight gain or loss over a period of time, but without being relegated to making rough guesses about calories consumed, through food and drink, and utilized, through normal body functions and exercises performed. Performance management software could play a similar cooperative role. Alternatively, an embodiment could be coupled with a calorie counting type of diet, so as to prevent the user from straying from reality (i.e., “that donut was only 50 calories,” or “I only had a half portion.”). Certain safety features could also be incorporated if a user was consuming too few calories over a period of time or exercising too much, such as by disabling the scanning device or sending a message to a central office so as to enable a person to check on the user.
While it is well known that blood glucose levels can be used to monitor caloric intake and utilization, no presently available glucose monitoring technology can be acceptably used for this purpose. To accurately monitor caloric levels, a subject would need to check their glucose level many times during the course of a day, such as when they first wake-up, eat something, exercise or travel to work, after they have a snack or are active for a period of time, before and after lunch, mid-day, sometime between leaving work and having dinner, perhaps before dinner and after dinner, before going to bed, etc. Consequently, a subject might realistically check their caloric level as many as 15 or 20 times during the course of each day. Existing continuous glucose monitoring devices cannot practically be used this many times each day and would be rejected by subjects for such purposes.
Although devices used to continuously self-monitor blood sugar levels have been available to the public for a few years, current continuous glucose monitors (CGMs) have a number of shortcomings and are impractical for weight and performance management applications. For example, data is stored and downloaded by a healthcare provider. Therefore, no glucose readout is immediately available to the patient, so on-the-spot corrections cannot be made. Also, current continuous, invasive blood glucose monitoring systems may use a needle sensor system, a micropore system, or a microdialysis system. The needle sensor system involves placing a needle under the skin, which sends data through a wire running through the skin to a monitor worn by the patient. To verify their accuracy, these devices require frequent calibration via finger stick tests.
Piercing the body, particularly the fingertips, to draw blood is painful. Lancing the fingertips several times during the course of a day can render the tips so sensitive that it restricts ordinary activities. In addition, studies investigating the long term damage caused by continual body lancing reveal a clear relationship between lancing frequency and skin changes, predominately thickening of the skin in the repeatedly lanced area (Fruhstorfer (2006) Practical Diabetes International 23: 207-209).
While for diabetics a finger stick to monitor blood sugar levels may seem like a minor nuisance compared to the complications that uncontrolled diabetes can cause, it is often enough to deter those subjects from testing their blood sugar levels as often as necessary. This being the case, subjects who are not combating a potentially debilitating disease, but who merely wish to monitor blood glucose levels to maintain a healthy weight or to maximize physical performance, would certainly be dissuaded from regularly monitoring their blood glucose levels using current technologies.
Consequently, there is a desire for a less invasive method of glucose measurement and monitoring for a variety of uses. Methods exist or are being developed for a minimally invasive glucose monitoring, which use body fluids other than blood (e.g., sweat, tears, or saliva) or subcutaneous fluid. Sweat and saliva are relatively easy to obtain, but their glucose concentration appears to lag in time significantly behind that of blood glucose. For that reason, tears, saliva and sweat have failed as viable matrices for use as surrogates for blood in monitoring glucose levels.
Other minimally invasive CGMs measure the glucose level of interstitial fluid utilizing a small catheter inserted between layers of skin. However, as with the blood samples of the minimally invasive blood glucose monitoring devices described above, glucose levels in interstitial fluid lag temporarily behind blood glucose values. Patients therefore require traditional finger stick measurements for calibration (typically twice a day) and are often advised to use finger stick measurements to confirm glucose levels. These systems are problematic in that temperature and perspiration can affect fluids in interstitial space and can subsequently influence the measurements.
Several companies have developed blood test products that are less invasive and require smaller blood volumes. With these products, blood can be drawn from other areas of the body such as the arms and legs. However, blood drawn from an arm or a leg using these products appears to more slowly reflect the changes in blood sugar than blood samples drawn from the fingertips. And although drawing blood from these alternate sites is less painful than drawing the blood from the nerve-rich fingertips, these products still require piercing the skin.
Current CGM technologies fall short of meeting the needs of diabetics whose lives would greatly benefit from continuous glucose monitoring. And while these technologies fail to meet the needs of those subjects most in need, they are even less adequate for subjects who simply wish to monitor their glucose levels so as either 1) to maintain a healthy weight, thereby reducing their risk of other physical complications, or 2) to maximize their physical performance.
For these subjects, permanently attached needles, catheters or monitors that restrict physical movement are unacceptable. Lag times between glucose values in alternate body fluids or in blood samples drawn from other parts of the body versus immediate glucose values are impractical. Measurements affected by temperature or perspiration are useless. Alternatively, immediate glucose readouts available to the patient so on-the-spot corrections can be made are essential.
Clearly, there is a bona fide need for a non-invasive, real-time, continuous blood glucose, lipid and electrolyte monitoring method to assist subjects in managing their weight as well as for performance management.